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Research Summary

The Arnsten lab studies molecular influences on higher cognitive function, with the aim of developing rational therapies for mental illness and for age-related cognitive disorders such as Alzheimer's Disease. The work focuses on the prefrontal cortex, a highly evolved brain region that creates our "Mental Sketchpad", allowing us abstract reasoning, high order decision-making, working memory, and thoughtful regulation of attention, behavior and emotion (including inhibition of inappropriate thoughts, actions and feelings). The Arnsten lab has discovered powerful chemical signaling pathways that can impair prefrontal function, e.g. when we are stressed, as well as protective pathways that maintain strong cognitive function. These pathways are altered by normal aging, and can be genetically altered in mental illness. Based on research in the Arnsten lab, two medications have been developed for human use: guanfacine (Intuniv) for the treatment of Attention Deficit Hyperactivity Disorder, and prazosin for the treatment of Post-Traumatic Stress Disorder.

Specialized terms: Molecular influences on higher cognitive function

Extensive Research Description

The Arnsten Lab studies molecular influences on the higher cognitive functions of the prefrontal cortex (PFC), with the overarching goal of developing rational treatments for cognitive disorders and mental illness. The lab uses a multi-disciplinary approach to understand mechanisms influencing working memory at the cellular and behavioral levels. Research has focused on how the arousal pathways rapidly alter PFC network strength through intracellular signaling mechanisms, a process termed Dynamic Network Connectivity. Our data explain how exposure to stress causes the rapid loss of PFC cognitive abilities, and how genetic mutations in molecules that regulate these pathways can lead to symptoms of mental illness. Dysregulation of these pathways with advancing age leads to loss of neuronal firing, cognitive impairments,and increased vulnerability for degeneration. Understanding these mechanisms has led to successful new treatments for patients with PFC dysfunction, including medications for Attention Deficit Hyperactivity Disorder, Post-Traumatic Stress Disorder and a potential treatment for schizophrenia and bipolar disorder.

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